[Electric activity of the brain at early and late clinical stages of experimental modeling of Parkinson's disease, an impact of hemantane].

Abstract: S.

Objective: To study an influence of the adamantane derivative hemantane on the electrical activity of the brain structures of mice at the early and late (severe) stages of experimental modeling of Parkinson's disease (PD).

Material And Methods: For experimental modeling of PD in C57BL/6J mice, 30 male C57BL/6J mice weighing 25-32 g were systemically (intraperitoneally) administered proneurotoxin MPTP in two modes corresponding to different clinical stages of the disease: 1-methyl-4-phenyl-1.

The neuroprotective effect of isatin in the rotenone-induced model of parkinonism in rats: the study of delayed effects.

Parkinsonism in rats induced by the pesticide rotenone is one of the most adequate models of Parkinson's disease (PD). Isatin (indole-2,3-dione) is an endogenous regulator found in mammals and humans and exhibiting a wide range of biological activities mediated by numerous isatin-binding proteins, including those associated with neurodegenerative pathology. A course of rotenone administration to rats caused behavioral impairments and changes in the profile and relative content of isatin-binding proteins in the brain.

The delayed effect of rotenone on the relative content of brain isatin-binding proteins of rats with experimental parkinsonism.

Isatin (indoldione-2,3) is an endogenous biological regulator found in the brain, peripheral tissues, and biological fluids of humans and animals. Its biological activity is realized via isatin-binding proteins, many of which were identified during proteomic profiling of the brain of mice and rats. A number of these proteins are related to the development of neurodegenerative diseases.

Neuroprotective effects of isatin and afobazole in rats with rotenone-induced Parkinsonism are accompanied by increased brain levels of Triton X-100 soluble alpha-synuclein.

Effects of the endogenous neuroprotector isatin and the pharmacological drug afobazole (exhibiting neuroprotective properties) on behavioral reactions and quantitative changes in the brain proteomic profile have been investigated in rats with experimental rotenone Parkinsonism. A single dose of isatin (100 mg/kg subcutaneously on the last day of a 7-day course of rotenone administration) improved the motor activity of rats with rotenone-induced Parkinsonism in the open field test (horizontal movements) and the rotating rod test. Afobazole (10 mg/kg intraperitoneally, daily during the 7-day course of rotenone administration) reduced the manifestations of rigidity and postural instability.

Quantitative changes of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism.

Isatin (indoldione-2,3) is an endogenous regulator found in humans and animals. It exhibits a broad range of biological activity mediated by numerous isatin-binding proteins. Isatin produces neuroprotective effects in several experimental models of diseases, including Parkinsonism induced by the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).

Experimental Study of Antidepressant Properties of Afobazole.

We studied the effects of oral administration of Afobazole in a dose of 10 mg/kg for 5 days on depressive-like behavior of male C57BL/6 mice in the tail suspension test in comparison with amitriptyline (10 mg/kg) or fluoxetine (20 mg/kg) treatment. Afobazole produced an antidepressant effect similar to amitriptyline, but inferior to fluoxetine. The σ1 receptor antagonist BD-1047 in a dose of 5 mg/kg blocked the antidepressant effect of Afobazole, which indicates the involvement of σ1 receptors in the antidepressant effect of the drug.

[Characteristics of behavioral reactions and the profile of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism].

The neurotoxins rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (МPTP) are used for modeling Parkinson's disease in animals (PD). They induce the mitochondrial respiratory chain dysfunction, which leads to the dopaminergic (DA) neuron degeneration. The advantage of the rotenone model consists in ability of rotenone to cause neurodegeneration showing symptoms and molecular biological characteristics similar to those of PD.

[Changes in the mitochondrial subproteome of mouse brain Rpn13-binding proteins induced by the neurotoxin MPTP and the neuroprotector isatin].

Mitochondrial dysfunction and ubiquitin-proteasome system (UPS) failure contribute significantly to the development of Parkinson's disease (PD). The proteasome subunit Rpn13 located on the regulatory (19S) subparticle play an important role in the delivery of proteins, subjected to degradation, to the proteolytic (20S) part of proteasome. We have previously found several brain mitochondrial proteins specifically bound to Rpn13 (Buneeva et al.

Afobazole Alleviates Cognitive Rigidity in Experimental Model of Autism Spectrum Disorders.

Afobazole (10 mg/kg) alleviated cognitive rigidity in BALB/c mice, a phenotypic model of autism spectrum disorders. It improved spatial memory and retraining in T-maze with drinking reinforcement and restored the retrieval of acquired skill during reversal learning in Morris water maze.

[The effect of a neuroprotective dose of isatin or deprenyl to mice on the profile of brain isatin-binding proteins].

Isatin (indol-2,3-dione), an endogenous biofactor found in the brain, peripheral tissues and biological body fluids of humans and animals, exhibits a wide range of biological and pharmacological activities. They are realized via interaction with numerous isatin-binding proteins. Some of these proteins identified during proteomic profiling of the brain are involved in the development of neurodegenerative pathology.

The Effect of Neurotoxin MPTP and Neuroprotector Isatin on the Profile of Ubiquitinated Brain Mitochondrial Proteins.

Mitochondria are a crucial target for the actions of neurotoxins, causing symptoms of Parkinson's disease in various experimental animal models, and also neuroprotectors. There is evidence that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria) and neuroprotective effects of certain anti-Parkisonian agents (monoamine oxidase inhibitors) may be associated with their effects on the UPS. In this study, we have investigated the effect of the neurotoxin MPTP and neuroprotector isatin, and their combination on the profile of ubiquitinated brain mitochondrial proteins.

[Effect of afobazole and levodopa on the activity of proline-specific proteinases and adenosine deaminase in blood serum and brain structures of rats with experimental Parkinson's syndrome induced by systemic administration of rotenone].

Rats with experimental Parkinson's syndrome induced by seven-day intraperitoneal administration of rotenone at a dose of 2.75 mg/kg have an increased activity of prolylendopeptidase (EC 3.4.

Activities of Proline-Specific Proteinases in the Serum and Cerebrospinal Fluid of Rats with the Fetal Valproate Syndrome.

In 60-day-old Wistar rats with fetal valproate syndrome, the brain to body weight ratio was higher by 9.4% and activity of dipeptidyl peptidase IV in the serum and cerebrospinal fluid was higher by 18.4 and 40.

Evolution of anti-parkinsonian activity of monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol in various in vivo models.

It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Diol) demonstrates high antiparkinsonian activity in some animal models. We carried out an extended study of the antiparkinsonian activity of Diol in a set of relevant animal models. Diol (20mg/kg) exhibited an anticataleptogenic effect in the haloperidol-induced catalepsy model and restored motor activity in animals in the reserpine-induced model of oligokinesia.

[The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins].

Isatin (indole-2,3-dione) is an endogenous indole found in the mammalian brain, peripheral organs and body fluids. It acts as a neuroprotector, which decreases manifestation of locomotor impairments in animal models of Parkinson's disease. A wide range of biological activity of isatin is associated with interaction of this regulator with numerous isatin-binding proteins.

[A comparative study of the effects of mexidolum and mildronatum on the physical performance of experimental animals].

Aim: To evaluate the effects of mexidolum on physical performance using acute and subchronic administration in experimental animals.

Material And Methods: The investigation was carried out using 123 male white outbred mice. The forced swim test was used to assess the effects of the drugs on the physical performance of mice.

Brain Mitochondrial Subproteome of Rpn10-Binding Proteins and Its Changes Induced by the Neurotoxin MPTP and the Neuroprotector Isatin.

Mitochondria play an important role in molecular mechanisms of neuroplasticity, adaptive changes of the brain that occur in the structure and function of its cells in response to altered physiological conditions or development of pathological disorders. Mitochondria are a crucial target for actions of neurotoxins, causing symptoms of Parkinson's disease in various experimental animal models, and also neuroprotectors. Good evidence exists in the literature that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria), and neuroprotective effects of certain antiparkinsonian agents (monoamine oxidase inhibitors) may be associated with their effects on UPS.

Anti-Parkinsonian Activity of Hemantane on a Model of Hemiparkinsonian Syndrome in Rats.

Hemantane demonstrated a pronounced antiparkinsonian activity in the model of hemiparkinsonian syndrome provoked in rats by unilateral intracerebral injection of 6-hydroxydopamine, which was comparable to efficacy of levodopa in decreasing the duration of cataleptogenic state and the degree of akinesia of the contralesional forelimb assessed in the cylinder test. In the stepping test, hemantane exerted a long-term effect in contrast to levodopa, which diminished its beneficial action to the treatment day 21. In the swing test, the behavior normalized only by hemantane.

Experimental investigation of pharmacodynamics and pharmacokinetics of carbamazepine nanoemulsion.

Anticonvulsant activity and pharmacokinetics of nanoemulsion and unmodified substance of carbamazepine were compared in experiments on mice. Carbamazepine nanoemulsion demonstrated significant anticonvulsant activity and was superior to unmodified substance of carbamazepine against seizures induced by maximum electric shock and picrotoxin. Relative bioavailability of carbamazepine after administration of nanoemulsion was 160% compared to unmodified substance.

Noopept normalizes parameters of the incretin system in rats with experimental diabetes.

Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that antihyperglycemic activity of an original nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under conditions of oral application than after intraperitoneal injection. These data provided a basis for studying the effect of Noopept on major indexes of the incretin system. Streptozotocin was shown to decrease the concentrations of incretin GLP-1 and insulin in the blood.

[Influence of hemantane in injectable dosage form on levodopa-induced dyskinesia in rats with model parkinsonian syndrome].

Levodopa-induced heavy dyskinesia was modeled in rats with severe hemiparkinsonian syndrome induced by injection of 6-hydroxydopamine in the left medial forebrain bundle. It is established that the antidyskinetic effect of the injectable dosage form of a new antiparkinsonian drug hemantane (5 mg/kg) after a single intravenous administration is weaker than that of the most effective in clinical practice antidyskinetic drug amantadine (20 mg/kg). However, after five days of treatment, the effect of hemantane injections exceeded that of amantadine.

Comparative activity of proline-containing dipeptide noopept and inhibitor of dipeptidyl peptidase-4 sitagliptin in a rat model of developing diabetes.

Developing diabetes was modeled on adult male Wistar rats by repeated intraperitoneal injections of streptozotocin in a subdiabetogenic dose of 30 mg/kg for 3 days. Proline-containing dipeptide drug Noopept or a standard diabetic drug dipeptidyl peptidase-4 inhibitor sitagliptin was administered per os in a dose of 5 mg/kg before each injection of the toxin and then for 16 days after streptozotocin course. In active control group, spontaneously increase glucose level and reduced tolerance to glucose load (1000 mg/kg intraperitoneally) were observed on the next day after the third administration of toxin.

[Effect of hemantane on bioelectric activity of brain in mice with MPTP-induced Parkinson syndrome].

A single intraperitoneal injection of MPTP neurotoxin (30 mg/kg) in C57BL/6 mice causes desynchronization of EEG with a decrease of theta-1 activity and a growth of beta activity in the interval of 15-30 Hz. Subchronic administration of the new antiparkinsonian drug hemantane (injection form) in a dose of 10 mg/kg makes the power of MPTP-induced beta oscillations less pronounced and leads to its reliable decrease within 24 h. This effect of hemantane administration was manifested during the entire period of observations.

Efficiency of noopept in streptozotocin-induced diabetes in rats.

We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin.

[Study of hemantane effects in rats on a model of early (premotor) stage of Parkinson's disease].

Presymptomatic (premotor) stage of Parkinson's disease has been modeled in rats by intranigral bilateral injections of neurotoxin MPTP. Three weeks after surgery, rats demonstrated cognitive deficit and depressive-like behavior without definite motor impairment. Pretreatment with hemantane (10 mg/kg) and the reference drug amantadine (20 mg/kg) 5 days before MPTP and further administration during 3 weeks after MPTP preserve cognitive function and prevented depressive disturbances in rats.